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1.
PLoS One ; 19(5): e0298828, 2024.
Article En | MEDLINE | ID: mdl-38809887

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides.


Fat Emulsions, Intravenous , Poisoning , Animals , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/therapeutic use , Fat Emulsions, Intravenous/adverse effects , Cats , Dogs , Retrospective Studies , Male , Female , Poisoning/therapy , Poisoning/diagnosis , Triglycerides/blood , Glasgow Coma Scale , Cat Diseases/drug therapy , Dog Diseases/drug therapy , Blood Gas Analysis
2.
Adv Rheumatol ; 64(1): 37, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702826

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.


Fat Emulsions, Intravenous , Gastrointestinal Hemorrhage , Gout , Hyperuricemia , Humans , Hyperuricemia/complications , Gout/complications , Gout/drug therapy , Male , Risk Factors , Female , Gastrointestinal Hemorrhage/etiology , Case-Control Studies , Retrospective Studies , Middle Aged , Fat Emulsions, Intravenous/adverse effects , Fat Emulsions, Intravenous/therapeutic use , Fat Emulsions, Intravenous/administration & dosage , Symptom Flare Up , Aged
3.
J Pediatr Surg ; 59(7): 1369-1373, 2024 Jul.
Article En | MEDLINE | ID: mdl-38614946

INTRODUCTION: Reducing soybean lipid emulsion (SLE) dose may prevent parenteral nutrition-associated cholestasis (PNAC) but effects on growth and neurodevelopment are unknown. The purpose of this study was to evaluate the effect of reduced dose SLE on growth and neurodevelopment. METHODS: Surgical neonates at 4 centers were randomized to standard SLE (3 g/kg/day) or reduced SLE (1 g/kg/day) over a 12-week period. Bilirubin levels and growth parameters were measured baseline and weekly while on study. The effects of time and group on direct bilirubin and growth were evaluated with a linear mixed effects model. Neurodevelopmental outcomes were assessed at 12- and 24-months corrected gestational age. RESULTS: Twenty-one individuals were randomized (standard dose = 9, reduced dose = 12). Subjects in the reduced dose group had slower rates of direct bilirubin increase and overall levels decreased earlier than those in the standard dose group. There was a trend toward a faster direct bilirubin decrease in the reduced dose group (p = 0.07 at day 84). There were no differences in the rates of change in weight (p = 0.352 at day 84) or height Z-scores (p = 0.11 at day 84) between groups. One subject in the reduced dose group had abnormal neurodevelopmental testing at 24 months. CONCLUSIONS: Surgical neonates randomized to a reduced dose of SLE had improved trends in direct bilirubin levels without clinically significant differences in overall growth and neurodevelopment. TYPE OF STUDY: Randomized Controlled Trial. LEVEL OF EVIDENCE: II.


Bilirubin , Cholestasis , Fat Emulsions, Intravenous , Parenteral Nutrition , Soybean Oil , Humans , Cholestasis/etiology , Cholestasis/prevention & control , Infant, Newborn , Soybean Oil/administration & dosage , Soybean Oil/therapeutic use , Female , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/therapeutic use , Parenteral Nutrition/adverse effects , Parenteral Nutrition/methods , Male , Bilirubin/blood , Infant , Infant, Premature , Dose-Response Relationship, Drug
5.
Rev. esp. anestesiol. reanim ; 69(7): 421-432, Ago.- Sep. 2022. ilus, tab
Article Es | IBECS | ID: ibc-207288

La emulsiones lipídicas intravenosas (ELI) se han utilizado ampliamente para el tratamiento de la intoxicación por anestésicos locales (AL) y se han propuesto como tratamiento de la intoxicación por otros fármacos. Sin embargo, el grado de evidencia de este tipo de terapias no es sólido, ya que proviene en su mayoría de casos clínicos. El objetivo de esta revisión narrativa es describir los mecanismos de acción propuestos para las ELI en la intoxicación por AL y otros fármacos, y evaluar los estudios recientes realizados en animales que sustentan las recomendaciones de su uso y la experiencia en humanos que apoyan el empleo de las ELI tanto en la intoxicación por AL como por otros fármacos. Para ello, se llevó a cabo una búsqueda en las bases de datos Embase, Medline, Cochrane y Google Scholar abarcando los artículos relevantes durante los últimos 10 años. En caso de intoxicación por AL, se recomienda aplicar los protocolos dictados por las guías internacionales, sabiendo que el grado de evidencia no es muy elevado. En la intoxicación por otros fármacos, las ELI están aconsejadas en situaciones graves inducidas por xenobióticos liposolubles que no responden al tratamiento estándar.(AU)


Intravenous lipid emulsions (ILEs) have been used widely for the treatment of local anesthetic (LA) poisoning and have been proposed as a treatment for intoxication by other drugs. However, the degree of evidence for this kind of therapy is not strong, as it comes mostly from clinical cases. The aim of this narrative review is to describe the proposed mechanisms of action for ILEs in poisoning by LA and other drugs and to evaluate recent studies in animals that support the recommendations for their use and the experience in humans that support the use of ILESs in both LA and other drug poisoning. For this purpose, a search was performed in the Embase, Medline and Google Scholar databases covering relevant articles over the last 10 years. In the case of AL poisoning, we recommend applying the protocols dictated by international guidelines, knowing that the degree of evidence is not very high. In poisoning by other drugs, ILEs are recommended in serious situations induced by liposoluble xenobiotics that do not respond to standard treatment.(AU)


Humans , Animals , Male , Female , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/therapeutic use , Poisoning/drug therapy , Anesthetics, Local/adverse effects , Anesthetics, Local/toxicity , Pharmaceutical Preparations , Toxicity/adverse effects , Toxicity/prevention & control , Fat Emulsions, Intravenous/pharmacology , Fat Emulsions, Intravenous/pharmacokinetics , Anesthesiology , Xenobiotics
6.
Clin Nutr ; 41(1): 80-90, 2022 01.
Article En | MEDLINE | ID: mdl-34864457

BACKGROUND: Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure in a community setting. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes. Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood. The aim of this study is to systematically review and evaluate the evidence for the differential effects of HPN solutions and to understand what features are associated with differences in clinical endpoints. METHODS: A systematic literature search was conducted between September and December 2020, and updated in July 2021 using the MEDLINE (Ovid), EMBASE, Scopus, and Web of Science databases. Studies were selected according to the following criteria (a) adult participants (>18 years old) dependent on HPN; (b) randomised controlled trials, prospective cohort and cross-sectional study designs; (c) primary research comparing two or more HPN solutions and (d) published in English language. Data were extracted and study quality assessed using Cochrane Collaboration's tools: Risk of Bias for Randomised Controlled Trials (RCTs); Risk of Bias in Non-Randomised Studies of Interventions; and the Newcastle Ottawa Scale for cross-sectional studies. RESULTS: Of the 5148 articles identified, seven RCTs, two prospective cohort and one cross-sectional study were included with a total of 295 participants. Studies varied in terms of duration (one to 60 months) and sample size (n = 5 to 88). Ten studies compared lipid emulsions (LE) and one study also compared LE with lipid-free HPN. No studies were found that compared the amino acid, vitamin, trace element or electrolyte components of HPN. In general, LE were well tolerated with no significant adverse effects. LE containing olive +/or fish oil were associated with a lower ω-6:ω-3 fatty acid ratio, positive reductions in markers of liver function, and changes in blood and cell fatty acid profiles. CONCLUSIONS: Despite the increasing use of HPN, there is surprisingly little evidence available to guide the provision of macro and micronutrients in the adult population requiring this therapy. Although LE containing olive +/or fish oil show promise with regards to liver function and blood and cell fatty acid profiles, further studies are needed before drawing definitive conclusions on the clinical value of these emulsions. It is likely that one type of HPN solution alone cannot be uniformly applied to patient care, and each patient should be assessed on an individual basis.


Fat Emulsions, Intravenous/administration & dosage , Intestinal Diseases/therapy , Parenteral Nutrition, Home , Biomarkers/blood , Cross-Sectional Studies , Endpoint Determination , Fatty Acids/blood , Female , Fish Oils/administration & dosage , Humans , Intestinal Diseases/blood , Male , Micronutrients/administration & dosage , Middle Aged , Nutrients/administration & dosage , Olive Oil/administration & dosage , Prospective Studies , Randomized Controlled Trials as Topic , Treatment Outcome
7.
Nutrients ; 13(12)2021 Nov 25.
Article En | MEDLINE | ID: mdl-34959793

Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: n = 41 and S-LE: n = 35) with 344 VEP measurements (SMOF-LE: n= 191 and S-LE n = 153). Values of N2 and P2 were not significantly different between the SMOF-LE and S-LE groups. A possible better treatment effect in the SMOF-LE group was seen as a trend toward a shorter latency, indicating faster neural conduction at around term-equivalent age. Prospective trials and follow-up studies are necessary in order to evaluate the potential positive effect of SMOF-LE on neuronal conduction and visual pathway maturation.


Evoked Potentials, Visual/drug effects , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/chemistry , Fish Oils/administration & dosage , Neural Conduction/drug effects , Female , Humans , Infant, Newborn , Infant, Premature/physiology , Male , Olive Oil/administration & dosage , Parenteral Nutrition , Retrospective Studies , Soybean Oil/administration & dosage , Triglycerides/administration & dosage
8.
Int J Med Sci ; 18(14): 3106-3111, 2021.
Article En | MEDLINE | ID: mdl-34400881

Background: We investigated the extent of growth of microorganisms with simultaneous administration of lipid emulsions with infusions for Total Parenteral Nutrition (TPN), assuming that the lipid emulsions contaminated with microorganisms are stagnant in a closed-type infusion device. We also investigated if bacterial growth can be prevented in the infusion device by flushing the inside of the infusion device with saline solution after the administration of lipid emulsion from the side tube in vitro setting. Methods: We made a preparation by adding Escherichia coli to the lipid emulsion and started the infusion simultaneously with the infusion solution for TPN and lipid emulsion with the piggyback method. Immediately after the completion of lipid emulsion infusion, we conducted flushing with saline solution. The volume of saline solution was none, 5, 10, or 20 mL at a flow rate of 1 mL/s. Infusion solution that was stagnant in the infusion device was collected immediately before completing the lipid emulsion infusion and 20 h after flushing, i.e., 24 h after starting the infusion for TPN, and the number of viable bacteria was determined. Results: The number of viable E. coli increased in the infusion device of all three species used in this experiment 24 h after starting the lipid emulsion infusion without flushing. We found that bacterial growth could be prevented through flushing with saline solution after the completion of lipid emulsion infusion and flushing out the stagnant infusion solution in the closed-type infusion device. Conclusions: We found that if E. coli was present in the closed-type infusion device, it would multiply. We also found that the number of viable bacteria varied according to the variety and internal structure of the closed-type infusion device as well as the liquid volume used for flushing, although flushing can prevent the growth of microorganisms. Proper management and manipulation of infusion is required to prevent infection.


Equipment Contamination/prevention & control , Escherichia coli/isolation & purification , Fat Emulsions, Intravenous/administration & dosage , Infusions, Intravenous/instrumentation , Parenteral Nutrition, Total/instrumentation , Escherichia coli/growth & development , Parenteral Nutrition, Total/methods
9.
MCN Am J Matern Child Nurs ; 46(6): 330-338, 2021.
Article En | MEDLINE | ID: mdl-34334660

ABSTRACT: Local anesthetic systemic toxicity (LAST) is a life-threatening event caused by elevated local anesthetic plasma concentration. It is often unrecognized or misdiagnosed. Peripartum women are at increased risk for toxicity due to pregnancy-related physiological changes. Rising serum drug levels can cause cellular level impairment of mitochondria and voltage-gated ion channels leading to a cascade of symptoms that can end in cardiac arrest. Local anesthetic systemic toxicity can mimic other maternal pathologies but may be considered if local anesthetics have been used. Published treatment guidelines for this event include lipid emulsion which is approved for use in pregnant women. We review LAST in the maternity care setting, published treatment protocols, management of maternity patients with toxicity, and recommendations to increase awareness among maternity care clinicians for this medical emergency.


Anesthesia, Local/adverse effects , Anesthetics, Local/adverse effects , Anesthetics, Local/toxicity , Drug-Related Side Effects and Adverse Reactions/diagnosis , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/therapeutic use , Labor, Obstetric , Anesthesia, Local/methods , Anesthetics, Local/administration & dosage , Drug-Related Side Effects and Adverse Reactions/etiology , Female , Humans , Maternal Health Services , Postpartum Period , Practice Guidelines as Topic , Pregnancy
10.
Nutrients ; 13(8)2021 Jul 26.
Article En | MEDLINE | ID: mdl-34444708

Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospital with corresponding individual medical records up to July 2020 were analyzed. Long-term neurodevelopmental outcomes were defined by the international classification of disease codes -9 or -10. The prevalence of diseases was compared between LIPO and SMOF groups at five and five years old and further analyzed by stratification of 1500 g birth weight. The LIPO and SMOF groups each included 1120 neonates. Epilepsy, cerebral palsy, developmental disorder and attention-deficit hyperactivity disorder (ADHD) were significantly decreased at age two years in the SMOF group, and epilepsy, language delay (LD), ADHD and autism spectrum disorder (ASD) were significantly decreased in the SMOF group at age five years. In children with birth weight < 1500 g, ADHD was decreased in the SMOF group at ages two and five years, and ASD was decreased in the SMOF group at age five years. In children with birth weight ≥ 1500 g, epilepsy, LD and ADHD were decreased in the SMOF group at age two years. LD was decreased in the SMOF group at age five years. We conclude that lipid emulsions with fish oil improve the neurodevelopmental outcomes of children born prematurely.


Fat Emulsions, Intravenous/administration & dosage , Fish Oils/administration & dosage , Infant, Premature , Neurodevelopmental Disorders/epidemiology , Olive Oil/administration & dosage , Phospholipids/administration & dosage , Sorbitol/administration & dosage , Soybean Oil/administration & dosage , Triglycerides/administration & dosage , Cerebral Palsy/epidemiology , Cerebral Palsy/prevention & control , Cross-Sectional Studies , Drug Combinations , Epilepsy/epidemiology , Epilepsy/prevention & control , Female , Humans , Infant , Infant, Newborn , Male , Neurodevelopmental Disorders/prevention & control , Retrospective Studies
11.
Clin Nutr ; 40(7): 4569-4578, 2021 07.
Article En | MEDLINE | ID: mdl-34229261

BACKGROUND & AIMS: Intravenous lipid emulsions in parenteral nutrition may cause different metabolic responses and immune effects in critically ill patients with sepsis. The aim of this study is to investigate the effects of different lipid emulsions on changes in concentrations of adipokine and cytokine and their relationship with mortality in patients. METHODS: Patients enrolled in this prospective, single-center, observational cohort study, were estimated to require more than ten days of parenteral nutrition. They were treated with soybean oil-based or olive oil-based parenteral lipid emulsions. Adipokine and cytokine concentrations of septic patients were determined at enrollment and ten days after, in accordance with the diagnostic criteria of SEPSIS-3. The concentrations levels were measured in an enzyme-linked immunosorbent assay. Mortality was analyzed using the Kaplan-Meier method and Cox regressions. RESULTS: Over a 25-month period, 145 patients were assessed for eligibility and consequently, 40 patients were analyzed. On admission, both groups had comparable physiological scores, comorbidities, malnutrition risk, anthropometric measurements, metabolic/hematologic biomarkers and concentrations of adipokines and cytokines (p > .05). Serum leptin, resistin, and cytokines (IL-6, IL-10, IL-1ß and TNF-α) decreased significantly in the entire cohort over ten days following sepsis (p < .05). Serum resistin decreased in both olive oil-based and soybean oil-based lipid emulsions groups. Serum adiponectin only decreased in soybean oil-based lipid emulsions group (p < .05). There was association between survival and percentage changes in adiponectin, resistin and visfatin concentrations (log rank test: p < .05). CONCLUSION: Adipokine and cytokine responses are affected by medical nutritional therapy in the sepsis process and adipokines may represent functional prognostic biomarkers in critically ill patients with sepsis.


Adipokines/blood , Critical Care/methods , Fat Emulsions, Intravenous/administration & dosage , Parenteral Nutrition/methods , Sepsis/therapy , Aged , Biomarkers/blood , Critical Care Outcomes , Critical Illness/mortality , Critical Illness/therapy , Cytokines/blood , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Nicotinamide Phosphoribosyltransferase/blood , Olive Oil/administration & dosage , Prognosis , Proportional Hazards Models , Prospective Studies , Resistin/blood , Sepsis/blood , Sepsis/mortality , Soybean Oil/administration & dosage
12.
Medicine (Baltimore) ; 100(25): e26426, 2021 Jun 25.
Article En | MEDLINE | ID: mdl-34160431

INTRODUCTION: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. MATERIALS AND METHODS: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of ω-3 fatty acids or a mixture of ω-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of ω-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion.The main objective is to determine whether 5 days administration of intravenous ω-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality.Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. DISCUSSION: Studies of ω-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.


Esophagectomy/rehabilitation , Fat Emulsions, Intravenous/administration & dosage , Fish Oils/administration & dosage , Postoperative Care/methods , Postoperative Complications/therapy , Adult , Combined Modality Therapy/methods , Double-Blind Method , Enteral Nutrition , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Female , Humans , Interleukin-6/blood , Interleukin-6/immunology , Male , Parenteral Nutrition/methods , Postoperative Complications/blood , Postoperative Complications/etiology , Postoperative Complications/immunology , Prospective Studies , Randomized Controlled Trials as Topic , Treatment Outcome
13.
Nutrients ; 13(3)2021 Mar 10.
Article En | MEDLINE | ID: mdl-33801970

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil-based lipid therapy should be implemented in order to successfully halt and reverse IFALD.


Fat Emulsions, Intravenous/administration & dosage , Fish Oils/administration & dosage , Intestinal Diseases/complications , Liver Diseases/prevention & control , Liver Diseases/therapy , Adult , Animals , Child , Cholestasis/prevention & control , Cholestasis/therapy , Fat Emulsions, Intravenous/adverse effects , Humans , Infant , Infant, Newborn , Infusions, Intravenous , Liver Diseases/etiology , Risk Factors , Soybean Oil/administration & dosage
14.
Curr Gastroenterol Rep ; 23(6): 8, 2021 Apr 15.
Article En | MEDLINE | ID: mdl-33860385

PURPOSE OF REVIEW: Pediatric intestinal failure is a complex condition requiring specialized care to prevent potential complications. In this article, we review the available evidence supporting recent advances in care for children with intestinal failure. RECENT FINDINGS: Multidisciplinary intestinal rehabilitation teams utilize medical and surgical management techniques to help patients achieve enteral autonomy (EA) while preventing and treating the complications associated with intestinal failure. Recent advances in lipid management strategies, minimization of intestinal failure associated liver disease, prevention of central line-associated blood stream infections, and loss of access, as well as development of promising new hormone analogue therapy have allowed promotion of intestinal adaptation. These advances have decreased the need for intestinal transplant. There have been recent advances in the care of children with intestinal failure decreasing morbidity, mortality, and need for intestinal transplantation. The most promising new therapies involve replacement of enteroendocrine hormones.


Enteral Nutrition , Intestinal Diseases/therapy , Short Bowel Syndrome/therapy , Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/methods , Child , Chronic Disease , Fat Emulsions, Intravenous/administration & dosage , Hormones/therapeutic use , Humans , Intestinal Diseases/diagnosis , Intestinal Diseases/etiology , Intestinal Diseases/rehabilitation , Intestinal Pseudo-Obstruction/diagnosis , Intestinal Pseudo-Obstruction/etiology , Intestinal Pseudo-Obstruction/rehabilitation , Intestinal Pseudo-Obstruction/therapy , Intestines/transplantation , Organ Transplantation , Parenteral Nutrition , Short Bowel Syndrome/diagnosis , Short Bowel Syndrome/etiology , Short Bowel Syndrome/rehabilitation
15.
PLoS One ; 16(3): e0247638, 2021.
Article En | MEDLINE | ID: mdl-33764994

CONTEXT: Obesity, is a state of chronic inflammation, characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism. We have defined the accompanying decreased Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), ovarian steroids and reduced pituitary response to Gonadotropin-releasing Hormone (GnRH) as Reprometabolic syndrome, a phenotype that can be induced in healthy normal weight women (NWW) by acute infusion of free fatty acids and insulin. OBJECTIVE: To identify potential mediators of insulin and lipid-related reproductive endocrine dysfunction. DESIGN, SETTING, PARTICIPANTS: Secondary analysis of crossover study of eumenorrheic reproductive aged women of normal Body Mass Index (BMI) (<25 kg/m2) at an academic medical center. INTERVENTION: Participants underwent 6-hour infusions of either saline/heparin or insulin plus fatty acids (Intralipid plus heparin), in the early follicular phase of sequential menstrual cycles, in random order. Euglycemia was maintained by glucose infusion. Frequent blood samples were obtained. MAIN OUTCOME MEASURES: Pooled serum from each woman was analyzed for cytokines, interleukins, chemokines, adipokines, Fibroblast Growth Factor-21 (FGF-21) and markers of endoplasmic reticulum (ER) stress (CHOP and GRP78). Wilcoxon signed-rank tests were used to compare results across experimental conditions. RESULTS: Except for Macrophage Inflammatory Protein-1ß (MIP-1ß), no significant differences were observed in serum levels of any of the inflammatory signaling or ER stress markers tested. CONCLUSION: Acute infusion of lipid and insulin, to mimic the metabolic syndrome of obesity, was not associated with an increase in inflammatory markers. These results imply that the endocrine disruption and adverse reproductive outcomes of obesity are not a consequence of the ambient inflammatory environment but may be mediated by direct lipotoxic effects on the hypothalamic-pituitary-ovarian (HPO) axis.


Fatty Acids, Nonesterified/administration & dosage , Hyperinsulinism/metabolism , Hyperlipidemias/metabolism , Insulin/administration & dosage , Metabolic Syndrome/metabolism , Signal Transduction , Academic Medical Centers , Adolescent , Adult , Body Mass Index , Cross-Over Studies , Cytokines/genetics , Cytokines/metabolism , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Fat Emulsions, Intravenous/administration & dosage , Female , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Follicle Stimulating Hormone/genetics , Follicle Stimulating Hormone/metabolism , Gene Expression , Genetic Fitness/drug effects , Genetic Fitness/genetics , Glucose Clamp Technique , Gonadotropin-Releasing Hormone/genetics , Gonadotropin-Releasing Hormone/metabolism , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Humans , Hyperinsulinism/chemically induced , Hyperinsulinism/genetics , Hyperinsulinism/pathology , Hyperlipidemias/chemically induced , Hyperlipidemias/genetics , Hyperlipidemias/pathology , Luteinizing Hormone/genetics , Luteinizing Hormone/metabolism , Metabolic Syndrome/chemically induced , Metabolic Syndrome/genetics , Metabolic Syndrome/pathology , Pituitary Gland/drug effects , Pituitary Gland/metabolism , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolism
16.
Clin Nutr ; 40(6): 4444-4448, 2021 06.
Article En | MEDLINE | ID: mdl-33526286

OBJECTIVES: To study the association of hypertriglyceridemia and of lipid tolerance with clinical and nutritional data in preterm infants receiving routine parenteral nutrition. DESIGN: We retrospectively studied 672 preterm infants (gestational age <32 weeks) with birth weight <1250 g, consecutively admitted to our NICU, born between 2004 and 2018. Selected prenatal data and interventions, parenteral intakes and diseases were considered. Hypertriglyceridemia was defined as plasma triglycerides >250 mg⋅dL-1. Lipid tolerance was defined as the ratio of plasma triglycerides to the intravenous lipid intake at the time of sampling. Variables associated to hypertriglyceridemia and to lipid tolerance were identified by multiple logistic and linear regression analyses. RESULTS: Hypertriglyceridemia occurred in 200 preterm infants (30%), ranging from 67% at 23 weeks to 16% at 31 weeks' gestation. In 138 infants (69%) hypertriglyceridemia occurred at a lipid intake of 2.5 g⋅kg-1 or less. Lipid tolerance was reduced especially in infants of less than 28 weeks' gestation (14.3 ± 9.3 vs 18.8 ± 10.2, respectively, p < 0.001). Lipid tolerance was negatively associated with respiratory distress syndrome (OR = -1.14, p = 0.011), patent ductus arteriosus (OR = -1.73, p < 0.001), small for gestational age (OR = -2.96, p < 0.001), intraventricular haemorrhage (OR = -3.96, p < 0.001), late onset sepsis (OR = -8.56, p = 0.039). CONCLUSION: Preterm infants on routine parenteral nutrition were able to tolerate markedly lower intravenous lipid intakes than the recommended target values of current guidelines. Lipid tolerance was associated with some of the major complication of prematurity, possibly at risk of developing hypertriglyceridemia.


Fat Emulsions, Intravenous/administration & dosage , Hypertriglyceridemia/epidemiology , Infant, Premature, Diseases/epidemiology , Infant, Very Low Birth Weight , Parenteral Nutrition , Triglycerides/blood , Birth Weight , Female , Gestational Age , Humans , Incidence , Infant, Newborn , Infant, Premature , Male , Retrospective Studies
17.
Nutrients ; 13(2)2021 Feb 04.
Article En | MEDLINE | ID: mdl-33557154

Total parenteral nutrition (TPN) is a life-saving intervention for infants that are unable to feed by mouth. Infants that remain on TPN for extended periods of time are at risk for the development of liver injury in the form of parenteral nutrition associated cholestasis (PNAC). Current research suggests the lipid component of TPN is a factor in the development of PNAC. Most notably, the fatty acid composition, vitamin E concentration, and presence of phytosterols are believed key mediators of lipid emulsion driven PNAC development. New emulsions comprised of fish oil and medium chain triglycerides show promise for reducing the incidence of PNAC in infants. In this review we will cover the current clinical studies on the benefit of fish oil and medium chain triglyceride containing lipid emulsions on the development of PNAC, the current constituents of lipid emulsions that may modulate the prevalence of PNAC, and potential new supplements to TPN to further reduce the incidence of PNAC.


Cholestasis/etiology , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/adverse effects , Liver Diseases/etiology , Parenteral Nutrition/adverse effects , Parenteral Nutrition/methods , Humans , Infant, Newborn
18.
Pediatr Surg Int ; 37(2): 247-256, 2021 Feb.
Article En | MEDLINE | ID: mdl-33388967

PURPOSE: Composite lipid emulsion (CLE) has been used for intestinal failure-associated liver disease (IFALD) to compensate for the disadvantages of soybean oil lipid emulsion (SOLE) or fish oil lipid emulsion (FOLE). However, the influence of its administration is unclear. We evaluated the effects of these emulsions on IFALD using a rat model of the short-bowel syndrome. METHODS: We performed jugular vein catheterization and 90% small bowel resection in Sprague-Dawley rats and divided them into four groups: control (C group), regular chow with intravenous administration of saline; and total parenteral nutrition co-infused with SOLE (SOLE group), CLE (CLE group) or FOLE (FOLE group). RESULTS: Histologically, obvious hepatic steatosis was observed in the SOLE and CLE groups but not the FOLE group. The liver injury grade of the steatosis and ballooning in the FOLE group was significantly better than in the SOLE group (p < 0.05). The TNF-α levels in the liver in the FOLE group were significantly lower than in the SOLE group (p < 0.05). Essential fatty acid deficiency (EFAD) was not observed in any group. CONCLUSION: Fish oil lipid emulsion attenuated hepatic steatosis without EFAD, while CLE induced moderate hepatic steatosis. The administration of CLE requires careful observation to prevent PN-induced hepatic steatosis.


Fat Emulsions, Intravenous/administration & dosage , Liver Failure/complications , Parenteral Nutrition/methods , Short Bowel Syndrome/prevention & control , Animals , Disease Models, Animal , Humans , Rats , Rats, Sprague-Dawley , Short Bowel Syndrome/etiology
19.
Expert Opin Drug Saf ; 20(3): 307-320, 2021 Mar.
Article En | MEDLINE | ID: mdl-33356650

Introduction: Intestinal failure-associated liver disease (IFALD) refers to hepatic dysfunction that results from prolonged parenteral nutrition (PN) use. IFALD is multifactorial in origin and remains a major cause of morbidity and mortality. Prior to 2004, IFALD was associated with mortality as high as 90% in infants who remained on PN greater than 1 year. The advent of new strategies for intravenous lipid emulsion (ILE) administration and improved catheter care now allow many patients to remain on PN and recover from this once fatal condition. Several additional treatment modalities are often used to further improve outcomes for IFALD patients and they are reviewed here.Areas covered: The etiology of IFALD is presented, as well as the rationale behind the use of ILEs that contain fish oil. Other management strategies are addressed, including the effects of several pharmacologic and nutritional interventions.Expert opinion: Like its etiology, the management of IFALD is multifactorial. Prompt recognition of patients at risk, avoiding macronutrient excess, and preventing central line associated bloodstream infections will improve outcomes. In patients who develop IFALD, the use of fish oil monotherapy seems to be efficacious. The most effective intervention, however, continues to be discontinuation of PN and achieving full enteral feedings.


Intestinal Diseases/therapy , Liver Diseases/etiology , Parenteral Nutrition/adverse effects , Animals , Fat Emulsions, Intravenous/administration & dosage , Fish Oils/administration & dosage , Humans , Infant , Liver Diseases/mortality , Liver Diseases/therapy , Parenteral Nutrition/methods
20.
Am J Perinatol ; 38(S 01): e92-e101, 2021 08.
Article En | MEDLINE | ID: mdl-32120418

OBJECTIVE: This study aimed to establish neonatal serum triglyceride (TG) level reference ranges during lipid infusion and correlate peak TG with neonatal outcomes. STUDY DESIGN: This is a retrospective review of 356 neonates with 696 TG measures obtained in four neonatal intensive care units between 2015 and 2017. TG was evaluated collectively to establish a reference range and a threshold limit. To analyze the effects of a higher TG threshold, neonates were categorized by their peak TG: <180 (TG<180), 180 to 400 (TG180-400), and > 400 mg/dL (TG>400). Univariable and multivariable regression models were constructed to compare peak TG to patient characteristic and clinical outcomes. RESULTS: The frequency of TG > 400 mg/dL was 5% and found only in neonates weighing < 1.5 kg. Neonates in the TG180-400 (n = 91) group were significantly lower in birth weight and gestational age, had lower 5-minute APGAR scores, and had increased ventilatory requirement when compared with neonates in the TG<180 (n = 240) group (all p < 0.001). The TG180-400 group had increased risk of severe intraventricular hemorrhage (p = 0.02) and bronchopulmonary dysplasia (p = 0.03). Elevated TG was associated with mortality (odds ratio [OR]: 14.4, p < 0.001) in univariable analysis, but the relationship weakened (OR: 4.4, p = 0.05) after adjusting for comorbidities in multivariable logistic regression. CONCLUSION: It is unclear if the adverse outcomes seen in neonates with higher peak TG were due to elevated TG alone, or whether illness severity predicted the increased TG. More prospective studies are needed to further delineate the relationships.


Fat Emulsions, Intravenous , Hypertriglyceridemia/mortality , Infant, Newborn/blood , Parenteral Nutrition , Triglycerides/blood , Birth Weight , Bronchopulmonary Dysplasia/blood , Bronchopulmonary Dysplasia/etiology , Cerebral Intraventricular Hemorrhage/blood , Cerebral Intraventricular Hemorrhage/etiology , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/adverse effects , Female , Gestational Age , Humans , Hypertriglyceridemia/complications , Infant, Small for Gestational Age , Intensive Care Units, Neonatal , Logistic Models , Male , Odds Ratio , Reference Values , Retrospective Studies , Risk Factors , Triglycerides/adverse effects
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